The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells.

Abstract:

:The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (hPR-A and hPR-B). In most cell contexts, hPR-B functions as a transcriptional activator of progesterone-responsive genes, whereas hPR-A functions as a transcriptional inhibitor of all steroid hormone receptors. We have created mutations within the carboxyl terminus of hPR which differentially effect the transcriptional activity of hPR-B in a cell- and promoter-specific manner. Analogous mutations, when introduced into hPR-A, have no effect on its ability to inhibit the transcriptional activity of other steroid hormone receptors. The observed differences in the structural requirements for hPR-B and hPR-A function suggest that transcriptional activation and repression by PR are mediated by two separate pathways within the cell. In support of this hypothesis, we have shown that hPR-A mediated repression of human estrogen receptor (hER) transcriptional activity is not dependent on hER expression level but depends largely on the absolute expression level of hPR-A. Thus, it appears that hPR-A inhibits hER transcriptional activity as a consequence of a noncompetitive interaction of hPR-A with either distinct cellular targets or different contact sites on the same target. We propose that hPR-A expression facilitates a ligand-dependent cross-talk among sex steroid receptor signaling pathways within the cell. It is likely, therefore, that alterations in the expression level of hPR-A or its cellular target can have profound effects on the physiological or pharmacological responses to sex steroid hormone receptor ligands.

journal_name

Mol Cell Biol

authors

Wen DX,Xu YF,Mais DE,Goldman ME,McDonnell DP

doi

10.1128/mcb.14.12.8356

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

8356-64

issue

12

eissn

0270-7306

issn

1098-5549

journal_volume

14

pub_type

杂志文章
  • Multivalent binding of p53 to the STAGA complex mediates coactivator recruitment after UV damage.

    abstract::The recruitment of transcriptional coactivators, including histone modifying enzymes, is an important step in transcription regulation. A typical activator is thought to interact with several cofactors, presumably in a sequential manner. The common use of several cofactors raises the question of how activators achieve...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01461-07

    authors: Gamper AM,Roeder RG

    更新日期:2008-04-01 00:00:00

  • Requirement for the Mitochondrial Pyruvate Carrier in Mammalian Development Revealed by a Hypomorphic Allelic Series.

    abstract::Glucose and oxygen are two of the most important molecules transferred from mother to fetus during eutherian pregnancy, and the metabolic fates of these nutrients converge at the transport and metabolism of pyruvate in mitochondria. Pyruvate enters the mitochondrial matrix through the mitochondrial pyruvate carrier (M...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00166-16

    authors: Bowman CE,Zhao L,Hartung T,Wolfgang MJ

    更新日期:2016-07-14 00:00:00

  • Nup214 is required for CRM1-dependent nuclear protein export in vivo.

    abstract::Nucleoporins mediate transport of macromolecules across the nuclear pore complex, yet the function of many individual nucleoporins is largely unresolved. To address this question, we depleted cells of the cytoplasmic nucleoporins Nup214/CAN and Nup358/RanBP2 by RNA interference. Depletion of Nup214 resulted in codeple...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00342-06

    authors: Hutten S,Kehlenbach RH

    更新日期:2006-09-01 00:00:00

  • Attenuation of late simian virus 40 mRNA synthesis is enhanced by the agnoprotein and is temporally regulated in isolated nuclear systems.

    abstract::Studies were performed to verify the physiological significance of attenuation in the life cycle of simian virus 40 and the role of agnoprotein in this process. For these purposes, nuclei were isolated at various times after infection and incubated in vitro in the presence of [alpha-32P]UTP under the standard conditio...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.6.1327

    authors: Hay N,Aloni Y

    更新日期:1985-06-01 00:00:00

  • NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release.

    abstract::Muscle wasting (cachexia) is a consequence of chronic diseases, such as cancer, and is associated with degradation of muscle proteins such as MyoD. The cytokines tumor necrosis factor alpha and gamma interferon induce muscle degeneration by activating the transcription factor NF-kappaB and its target genes. Here, we s...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.15.6533-6545.2005

    authors: Di Marco S,Mazroui R,Dallaire P,Chittur S,Tenenbaum SA,Radzioch D,Marette A,Gallouzi IE

    更新日期:2005-08-01 00:00:00

  • Evolutionary conservation and predicted structure of the Drosophila extra sex combs repressor protein.

    abstract::The Drosophila extra sex combs (esc) protein, a member of the Polycomb group (PcG), is a transcriptional repressor of homeotic genes. Genetic studies have shown that esc protein is required in early embryos at about the time that other PcG proteins become engaged in homeotic gene repression. The esc protein consists p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.11.6663

    authors: Ng J,Li R,Morgan K,Simon J

    更新日期:1997-11-01 00:00:00

  • 5-fluorouracil enhances exosome-dependent accumulation of polyadenylated rRNAs.

    abstract::The antimetabolite 5-fluorouracil (5FU) is a widely used chemotherapeutic for the treatment of solid tumors. Although 5FU slows DNA synthesis by inhibiting the ability of thymidylate synthetase to produce dTMP, the drug also has significant effects on RNA metabolism. Recent genome-wide assays for 5FU-induced haploinsu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.24.10766-10776.2004

    authors: Fang F,Hoskins J,Butler JS

    更新日期:2004-12-01 00:00:00

  • Genetic rescue of muscle defects associated with a mutant Drosophila melanogaster tropomyosin allele.

    abstract::We describe a genetic transformation system which should prove useful for investigating tropomyosin assembly and function. Muscle abnormalities associated with a defective tropomyosin allele were corrected by integrating the wild-type gene into germ line chromosomes. The transformation protocol permits application of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.8.2977

    authors: Fyrberg EA,Karlik CC

    更新日期:1987-08-01 00:00:00

  • Ligand-independent phosphorylation of the glucocorticoid receptor integrates cellular stress pathways with nuclear receptor signaling.

    abstract::Glucocorticoids are stress hormones that maintain homeostasis through gene regulation mediated by nuclear receptors. We have discovered that other cellular stressors are integrated with glucocorticoid signaling through a new hormone-independent phosphorylation site, Ser134, on the human glucocorticoid receptor (GR). S...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05866-11

    authors: Galliher-Beckley AJ,Williams JG,Cidlowski JA

    更新日期:2011-12-01 00:00:00

  • Multiple pathways promote short-sequence recombination in Saccharomyces cerevisiae.

    abstract::In the budding yeast Saccharomyces cerevisiae, null alleles of several DNA repair and recombination genes confer defects in recombination that grow more severe with decreasing sequence length, indicating that they are required for short-sequence recombination (SSR). RAD1 and RAD10, which encode the subunits of the str...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.15.5347-5356.2002

    authors: Manthey GM,Bailis AM

    更新日期:2002-08-01 00:00:00

  • Beta-like importins mediate the nuclear translocation of mitogen-activated protein kinases.

    abstract::The rapid nuclear translocation of signaling proteins upon stimulation is important for the regulation of de novo gene expression. We have studied the stimulated nuclear shuttling of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) and found that they translocate into the nucleus in a Ra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,收录出版

    doi:10.1128/MCB.00799-13

    authors: Zehorai E,Seger R

    更新日期:2014-01-01 00:00:00

  • Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins.

    abstract::E6-AP is a 100-kDa cellular protein that mediates the interaction of the human papillomavirus type 16 and 18 E6 proteins with p53. The association of p53 with E6 and E6-AP promotes the specific ubiquitination and subsequent proteolytic degradation of p53 in vitro. We recently isolated a cDNA encoding E6-AP and have no...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.8.4918

    authors: Huibregtse JM,Scheffner M,Howley PM

    更新日期:1993-08-01 00:00:00

  • Delimiting regulatory sequences of the Drosophila melanogaster Ddc gene.

    abstract::We delimited sequences necessary for in vivo expression of the Drosophila melanogaster dopa decarboxylase gene Ddc. The expression of in vitro-altered genes was assayed following germ line integration via P-element vectors. Sequences between -209 and -24 were necessary for normally regulated expression, although genes...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.12.4548

    authors: Hirsh J,Morgan BA,Scholnick SB

    更新日期:1986-12-01 00:00:00

  • The N-terminal 24 amino acids of the p55 gamma regulatory subunit of phosphoinositide 3-kinase binds Rb and induces cell cycle arrest.

    abstract::Although phosphoinositide 3-kinase (PI 3-kinase) is essential for cell cycle progression, the molecular mechanisms that regulate its diverse biological effects are poorly understood. We demonstrate here that Rb, a key regulator of cell cycle progression, associates with p55 kDa (p55alpha and p55gamma) regulatory subun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.5.1717-1725.2003

    authors: Xia X,Cheng A,Akinmade D,Hamburger AW

    更新日期:2003-03-01 00:00:00

  • Differential and inefficient splicing of a broadly expressed Drosophila erect wing transcript results in tissue-specific enrichment of the vital EWG protein isoform.

    abstract::In this report, we document an unusual mode of tissue-enriched gene expression that is primarily mediated by alternative and inefficient splicing. We have analyzed posttranscriptional regulation of the Drosophila erect wing gene, which provides a vital neuronal function and is essential for the formation of certain mu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.6.3998

    authors: Koushika SP,Soller M,DeSimone SM,Daub DM,White K

    更新日期:1999-06-01 00:00:00

  • The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.

    abstract::A set of growth arrest-specific genes (gas) whose expression is negatively regulated after serum induction has previously been described (C. Schneider, R. M. King, and L. Philipson, Cell 54:787-793, 1988). The detailed analysis of one of them, gas6, is reported here, gas6 mRNA (2.6 kb) is abundantly expressed in serum...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.8.4976

    authors: Manfioletti G,Brancolini C,Avanzi G,Schneider C

    更新日期:1993-08-01 00:00:00

  • The mitogenic response to tumor necrosis factor alpha requires c-Jun/AP-1.

    abstract::In the present study, we addressed the role of the c-jun proto-oncogene in the mitogenic response of human fibroblasts and primary acute myelogenous leukemia blasts to tumor necrosis factor alpha (TNF-alpha). Our data indicate that TNF-alpha treatment of these cells is associated with transcriptional activation of c-j...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.7.4284

    authors: Brach MA,Gruss HJ,Sott C,Herrmann F

    更新日期:1993-07-01 00:00:00

  • E1A-mediated repression of progesterone receptor-dependent transactivation involves inhibition of the assembly of a multisubunit coactivation complex.

    abstract::The steroid hormone progesterone acts via high-affinity nuclear receptors that interact with specific DNA sequences located near the promoter of the hormone-responsive gene. Recent studies suggested that the hormone-occupied progesterone receptor (PR) mediates gene activation by recruiting a cellular coregulatory fact...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.6.2138-2146.2000

    authors: Xu Y,Klein-Hitpass L,Bagchi MK

    更新日期:2000-03-01 00:00:00

  • The Histone Variant MacroH2A Blocks Cellular Reprogramming by Inhibiting Mesenchymal-to-Epithelial Transition.

    abstract::Transcription factor-induced reprogramming of somatic cells to pluripotency is mediated via profound alterations in the epigenetic landscape. The histone variant macroH2A1 (mH2A1) is a barrier to the cellular reprogramming process. We demonstrate here that mH2A1 blocks reprogramming and contributes to the preservation...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00669-17

    authors: Pliatska M,Kapasa M,Kokkalis A,Polyzos A,Thanos D

    更新日期:2018-04-30 00:00:00

  • ZFP100, a component of the active U7 snRNP limiting for histone pre-mRNA processing, is required for entry into S phase.

    abstract::Metazoan replication-dependent histone mRNAs are the only eukaryotic mRNAs that are not polyadenylated. The cleavage of histone pre-mRNA to form the unique 3' end requires the U7 snRNP and the stem-loop binding protein (SLBP) that binds the 3' end of histone mRNA. U7 snRNP contains three novel proteins, Lsm10 and Lsm1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00391-06

    authors: Wagner EJ,Marzluff WF

    更新日期:2006-09-01 00:00:00

  • Different protein kinase C isoforms determine growth factor specificity in neuronal cells.

    abstract::Although mitogenic and differentiating factors often activate a number of common signaling pathways, the mechanisms leading to their distinct cellular outcomes have not been elucidated. In a previous report, we demonstrated that mitogen-activated protein (MAP) kinase (ERK) activation by the neurogenic agents fibroblas...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.15.5392-5403.2000

    authors: Corbit KC,Soh JW,Yoshida K,Eves EM,Weinstein IB,Rosner MR

    更新日期:2000-08-01 00:00:00

  • HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells.

    abstract::The homeobox gene HOXA9 has recently been shown to be an important regulator of endothelial cell (EC) differentiation and activation in addition to its role in embryonic development and hematopoiesis. In this report, we have determined that the EC-leukocyte adhesion molecule E-selectin is a key target for HOXA9. The d...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00052-07

    authors: Bandyopadhyay S,Ashraf MZ,Daher P,Howe PH,DiCorleto PE

    更新日期:2007-06-01 00:00:00

  • Suppression of the progression phenotype in somatic cell hybrids occurs in the absence of altered adenovirus type 5 gene expression.

    abstract::In the present study we have analyzed the genetic regulation of increased expression of transformation-associated traits, a process termed progression, in adenovirus type 5 (Ad5)-transformed secondary rat embryo cells. Somatic cell hybrids were formed between a highly progressed neomycin-resistant Ad5-transformed clon...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.5.2027

    authors: Duigou GJ,Babiss LE,Iman DS,Shay JW,Fisher PB

    更新日期:1990-05-01 00:00:00

  • The K-fgf/hst oncogene induces transformation through an autocrine mechanism that requires extracellular stimulation of the mitogenic pathway.

    abstract::The K-fgf/hst oncogene encodes a secreted growth factor of the fibroblast growth factor (FGF) family. The ability of K-fgf-transformed cells to grow in soft agar and in serum-free medium is inhibited by anti-K-FGF neutralizing antibodies, consistent with an autocrine mechanism of transformation. The transformed proper...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.2.1138

    authors: Talarico D,Basilico C

    更新日期:1991-02-01 00:00:00

  • Developmental expression and 5S rRNA-binding activity of Xenopus laevis ribosomal protein L5.

    abstract::Ribosomal protein L5 binds specifically to 5S rRNA to form a complex that is a precursor to 60S subunit assembly in vivo. Analyses in yeast cells, mammalian cells, and Xenopus embryos have shown that the accumulation of L5 is not coordinated with the expression of other ribosomal proteins. In this study, the primary s...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.12.5281

    authors: Wormington WM

    更新日期:1989-12-01 00:00:00

  • MafB Is Important for Pancreatic β-Cell Maintenance under a MafA-Deficient Condition.

    abstract::The pancreatic-islet-enriched transcription factors MafA and MafB have unique expression patterns in β cells in rodents. MafA is specifically expressed in β cells and is a key regulatory factor for maintaining adult β-cell function, whereas MafB plays an essential role in β-cell development during embryogenesis, and i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00080-19

    authors: Xiafukaiti G,Maimaiti S,Ogata K,Kuno A,Kudo T,Shawki HH,Oishi H,Takahashi S

    更新日期:2019-08-12 00:00:00

  • Identification of histone mutants that are defective for transcription-coupled nucleosome occupancy.

    abstract::Our previous studies of Saccharomyces cerevisiae described a gene repression mechanism where the transcription of intergenic noncoding DNA (ncDNA) (SRG1) assembles nucleosomes across the promoter of the adjacent SER3 gene that interfere with the binding of transcription factors. To investigate the role of histones in ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05195-11

    authors: Hainer SJ,Martens JA

    更新日期:2011-09-01 00:00:00

  • Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase.

    abstract::Nucleolin is a ubiquitous multifunctional protein involved in preribosome assembly and associated with both nucleolar chromatin in interphase and nucleolar organizer regions on metaphasic chromosomes in mitosis. Extensive nucleolin phosphorylation by a casein kinase (CKII) occurs on serine in growing cells. Here we re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.7.3607

    authors: Belenguer P,Caizergues-Ferrer M,Labbé JC,Dorée M,Amalric F

    更新日期:1990-07-01 00:00:00

  • SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(-) cotransporter 2.

    abstract::Proper control of NaCl excretion in the kidney is central to bodily functions, yet many mechanisms that regulate reabsorption of sodium and chloride in the kidney remain incompletely understood. Here, we identify an important role played by the intracellular sorting receptor SORLA (sorting protein-related receptor wit...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01560-09

    authors: Reiche J,Theilig F,Rafiqi FH,Carlo AS,Militz D,Mutig K,Todiras M,Christensen EI,Ellison DH,Bader M,Nykjaer A,Bachmann S,Alessi D,Willnow TE

    更新日期:2010-06-01 00:00:00

  • c-Myc is required for the formation of intestinal crypts but dispensable for homeostasis of the adult intestinal epithelium.

    abstract::In self-renewing tissues such as the skin epidermis and the bone marrow, Myc proteins control differentiation of stem cells and proliferation of progenitor cell types. In the epithelium of the small intestine, we show that c-Myc and N-Myc are expressed in a differential manner. Whereas c-Myc is expressed in the prolif...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.17.7868-7878.2005

    authors: Bettess MD,Dubois N,Murphy MJ,Dubey C,Roger C,Robine S,Trumpp A

    更新日期:2005-09-01 00:00:00